Twelve-month efficacy and safety of omidenepag isopropyl, a selective EP2 agonist, in open-angle glaucoma and ocular hypertension: the RENGE study.

PURPOSE To assess the long-term safety and efficacy of omidenepag isopropyl (OMDI) 0.002% (a first-in-class, selective, non-prostaglandin, prostanoid EP2 receptor agonist), alone or administered concomitantly with timolol 0.5%, in patients with open-angle glaucoma (OAG, including normal-tension and exfoliation glaucoma) or ocular hypertension (OHT). STUDY DESIGN Open-label, multicenter, Phase 3 study (NCT02822729). METHODS Patients aged ≥ 20 years, with OAG or OHT, and a baseline diurnal intraocular pressure (IOP) ≥ 16- < 22 mmHg (Group 1) or ≥ 22- ≤ 34 mmHg (Groups 2 and 3) were enrolled. All patients (N = 125) received OMDI 0.002% once daily. Group 3 also received timolol 0.5% twice daily. IOP was measured at baseline and at Weeks 2, 4, 8, 12, 26, 40, and 52. RESULTS Significant reductions in mean diurnal IOP from baseline occurred at every visit (P < 0.0001). Mean ± SE diurnal IOP reduction at Week 52 was -3.7 ± 0.3 mmHg (Group 1), -5.6 ± 0.5 mmHg (Group 2), and -8.4 ± 0.6 mmHg (Group 3). Most adverse events (AEs) were mild, and no serious treatment-related AEs were reported. Conjunctival hyperemia (incidence: monotherapy [Groups 1 and 2], 18.8%; concomitant [Group 3], 45.0%) and macular edema (ME)/cystoid macular edema (CME) (incidence: monotherapy, 11.8%; concomitant, 15.0%) occurred most frequently. All treatment-related ME/CME cases occurred in pseudophakic eyes and responded to standard-of-care treatment and study drug discontinuation. CONCLUSIONS In this study, OMDI 0.002%, alone or administered concomitantly with timolol 0.5%, resulted in sustained IOP reduction over 52 weeks in patients with OAG or OHT. Concomitant treatment resulted in increased efficacy and increased incidence of conjunctival hyperemia.